Fatty acids are aliphatic acids fundamental to energy production and storage, cellular structure and as intermediates in the biosynthesis of hormones and other biologically important molecules. They are synthesized by a series of decarboxylative Claisen condensation reactions from acetyl-CoA and malonyl-CoA. Following each round of elongation, the beta keto group is reduced to the fully saturated carbon chain by the sequential action of a ketoreductase, a dehydratase, and an enol reductase. The growing fatty acid chain is carried between these active sites while attached covalently to the phosphoantetheine prosthetic group of an acyl carrier protein (ACP), and is released by the action of a thioesterase (TE) upon reaching a carbon chain length of 16. FIG. 1 shows a simplified diagram of fatty acid synthesis in E. coli. 
There are two principal classes of fatty acid synthases. Type I systems utilize a single large, multifunctional polypeptide. A Type I fatty acid synthase system is also found in the CMN group of bacteria (Corynebacteria, Mycobacteria, and Nocardia). In these bacteria, the FAS I system produces palmititic acid, and cooperates with the FASII system to produce a greater diversity of lipid products.
Type II fatty acid synthases (FASII) are found in prokaryotes, plants, fungi, and parasites, as well as in mitochondria. FASII is characterized by the use of the discrete, monofunctional enzymes for fatty acid synthesis. In contrast to the complex Type I fatty acid synthase that catalyzes multiple enzymatic steps, FASII uses individual enzymes to carry out the same steps.
The enzyme 3-oxoacyl-ACP reductase (or beta-ketoacyl-ACP reductase) uses NADPH as the coenzyme to carry out the following reaction (from BRENDA Enzyme Database):3-oxoacyl-ACP+NADPH+H+(3R)-3-hydroxyacyl-ACP+NADP+
However, the intracellular concentration of NADP+ and NADPH is much lower than that of NAD+ and NADH (Fuhrer and Sauer, 2009). Thus, at high fatty acid production rates, the NADPH availability can become a limiting factor, slowing production rates and overall accumulation.
Various strategies have been studied to increase NADPH availability in order to increase fatty acid productivity. These approaches have included: 1) the overexexpression of a transhydrogenase enzyme that transfers the reducing power from NADH to NADPH (Sanchez et al., 2006), 2) the overexexpression of NAD+ kinase to increase the NADP concentration (Wang et al., 2013), or 3) the replacement of the native NAD+ dependent glyceraldehyde-3-phosphate dehydrogenase (Gap) with a NADP+ dependent Gap (Martínez et al., 2008).
However, there is always room for further improvement in this area, particularly as petroleum resources become scarce and as the need to address environmental impact of non-renewable resources becomes critical. Thus, what is needed in the art are improved methods of producing fatty acids in bacteria, which is a renewable, relatively clean source of feedstock chemicals.